Inhibition of xanthine oxidase to prevent statin-induced myalgia and rhabdomiolysis

Atherosclerosis. 2015 Mar;239(1):38-42. doi: 10.1016/j.atherosclerosis.2014.12.055. Epub 2014 Dec 31.

Abstract

Although statins remain the cornerstone of lipid-lowering therapy for reducing the burden of atherosclerotic vascular disease, their administration has been associated with muscle-related adverse effects, including myalgia and rhabdomyolysis. Such adverse events are probably due to reduced antioxidant defenses associated with fewer intermediate metabolites in the cholesterol synthesis pathway. We hypothesize that the concomitant inhibition of xanthine oxidase via coadministration of allopurinol with statins could diminish reactive oxygen species (ROS)-related muscle damage, which would have in turn have positive effects on both the incidence of muscle-related adverse events and cardiovascular outcomes. Accordingly, inhibition of xanthine oxidase has been previously shown to be effective for reducing biomarkers of muscle damage following exercise in professional athletes. Because of the widespread statin utilization and increasing trends in their therapeutic use in atherosclerotic vascular diseases, the proposed strategy could have important clinical implications for reducing statin-induced myalgia and rhabdomyolysis.

Keywords: Allopurinol; Lipid-lowering drugs; Myalgia; Rhabdomyolysis; Xanthine oxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / therapeutic use
  • Animals
  • Biomarkers / metabolism
  • Cardiovascular Diseases / metabolism
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / drug therapy
  • Myalgia / chemically induced
  • Myalgia / drug therapy*
  • Myalgia / prevention & control*
  • Reactive Oxygen Species
  • Rhabdomyolysis / chemically induced
  • Rhabdomyolysis / drug therapy*
  • Rhabdomyolysis / prevention & control*
  • Ubiquinone / metabolism
  • Xanthine Oxidase / antagonists & inhibitors*

Substances

  • Biomarkers
  • Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Reactive Oxygen Species
  • Ubiquinone
  • Allopurinol
  • Xanthine Oxidase